Obesity is a potential risk factor for cognitive deficits in the elder humans. Using a high-fat diet (HFD)–induced obese mouse model, we investigated the impacts of HFD on obesity, metabolic and ...stress hormones, learning performance, and hippocampal synaptic plasticity. Both male and female C57BL/6J mice fed with HFD (3 weeks to 9–12 months) gained significantly more weights than the sex-specific control groups. Compared with the obese female mice, the obese males had similar energy intake but developed more weight gains. The obese male mice developed hyperglycemia, hyperinsulinemia, hypercholesterolemia, and hyperleptinemia, but not hypertriglyceridemia. The obese females had less hyperinsulinemia and hypercholesterolemia than the obese males, and no hyperglycemia and hypertriglyceridemia. In the contextual fear conditioning and step-down passive avoidance tasks, the obese male, but not female, mice showed poorer learning performance than their normal counterparts. These learning deficits were not due to sensorimotor impairment as verified by the open-field and hot-plate tests. Although, basal synaptic transmission characteristics (input–output transfer and paired-pulse facilitation (PPF) ratio) were not significantly different between normal and HFD groups, the magnitudes of synaptic plasticity (long-term potentiation (LTP) and long-term depression (LTD)) were lower at the Schaffer collateral-CA1 synapses of the hippocampal slices isolated from the obese male, but not female, mice, as compared with their sex-specific controls. Our results suggest that male mice are more vulnerable than the females to the impacts of HFD on weight gains, metabolic alterations and deficits of learning, and hippocampal synaptic plasticity.
Serotonin neurons located in the raphe nucleus of the hindbrain have crucial roles in regulating brain functions and have been implicated in various psychiatric disorders. Yet functional human ...serotonin neurons are not available for in vitro studies. Through manipulation of the WNT pathway, we demonstrate efficient differentiation of human pluripotent stem cells (hPSCs) to cells resembling central serotonin neurons, primarily those located in the rhombomeric segments 2-3 of the rostral raphe, which participate in high-order brain functions. The serotonin neurons express a series of molecules essential for serotonergic development, including tryptophan hydroxylase 2, exhibit typical electrophysiological properties and release serotonin in an activity-dependent manner. When treated with the FDA-approved drugs tramadol and escitalopram oxalate, they release or uptake serotonin in a dose- and time-dependent manner, suggesting the utility of these cells for the evaluation of drug candidates.
Microglia are emerging as key drivers of neurological diseases. However, we lack a systematic understanding of the underlying mechanisms. Here, we present a screening platform to systematically ...elucidate functional consequences of genetic perturbations in human induced pluripotent stem cell-derived microglia. We developed an efficient 8-day protocol for the generation of microglia-like cells based on the inducible expression of six transcription factors. We established inducible CRISPR interference and activation in this system and conducted three screens targeting the 'druggable genome'. These screens uncovered genes controlling microglia survival, activation and phagocytosis, including neurodegeneration-associated genes. A screen with single-cell RNA sequencing as the readout revealed that these microglia adopt a spectrum of states mirroring those observed in human brains and identified regulators of these states. A disease-associated state characterized by osteopontin (SPP1) expression was selectively depleted by colony-stimulating factor-1 (CSF1R) inhibition. Thus, our platform can systematically uncover regulators of microglial states, enabling their functional characterization and therapeutic targeting.
Dysregulation of neuronal excitability underlies the pathogenesis of tauopathies, including frontotemporal dementia (FTD) with tau inclusions. A majority of FTD-causing tau mutations are located in ...the microtubule-binding domain, but how these mutations alter neuronal excitability is largely unknown. Here, using CRISPR/Cas9-based gene editing in human pluripotent stem cell (iPSC)-derived neurons and isogenic controls, we show that the FTD-causing V337M tau mutation impairs activity-dependent plasticity of the cytoskeleton in the axon initial segment (AIS). Extracellular recordings by multi-electrode arrays (MEAs) revealed that the V337M tau mutation in human neurons leads to an abnormal increase in neuronal activity in response to chronic depolarization. Stochastic optical reconstruction microscopy of human neurons with this mutation showed that AIS plasticity is impaired by the abnormal accumulation of end-binding protein 3 (EB3) in the AIS submembrane region. These findings expand our understanding of how FTD-causing tau mutations dysregulate components of the neuronal cytoskeleton, leading to network dysfunction.
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•The FTD-causing V337M tau mutation impairs axon initial segment (AIS) plasticity•The V337M tau mutation impairs activity homeostasis•The V337M tau mutation leads to accumulation of EB3 in the AIS•EB3 is critical for regulating AIS plasticity and activity homeostasis
Frontotemporal dementia (FTD) with tau pathology is associated with aberrant hyperexcitability of neuronal networks. In human iPSC-derived neurons, Sohn et al. demonstrates that FTD-causing tau mutation abolishes activity-dependent plasticity of the axon initial segment and impairs homeostasis of neuronal activity via impacting AIS cytoskeleton, resulting in dysregulation of neuronal network function.
This study examines the effects of technology-enhanced interventions in hospitality curricula using an overarching research hypothesis - Does a course that features multi-model inputs, web-based ...learning opportunities and interactive communications prepare students well for their internships? Through an exploration of various influences within blended learning, this study unpacks students' responses to the pedagogical design, technology-enhanced interactions and in turn, assess for their intercultural competencies. The theoretical framework informing this study confirms the hypothesis that these multifaceted classroom activities demonstrated pedagogical effectiveness for knowledge retention. The findings showed that students' intercultural competences were significantly promoted. Students' learning interactions also improved due to the processes of video-making, sharing and discussions in the classroom. Moreover, these classroom activities significantly raised students' intercultural awareness. With regards to the effectiveness of the course for internship preparation, students showed moderate levels of satisfaction. Theoretical and practical contributions to the embedding of ICT within hospitality courses are provided.
Previous research has demonstrated a link between maternal depressive symptoms and infant feeding behavior; however, the underlying mechanisms linking the two remain unclear. This study examined the ...association between maternal depressive symptoms and responsive feeding, and the potential mediating role of feeding self-efficacy and outcome expectancy. A panel study with 487 women, from pregnancy through postpartum, was conducted. Maternal depressive symptoms at one month postpartum were assessed by the Edinburgh Postnatal Depression Scale. Responsive feeding included feeding on demand and unforced feeding domains. Responsive feeding, feeding self-efficacy, and feeding outcome expectancy were assessed at three months postpartum. Maternal depressive symptoms were associated with less responsive feeding, but the association was fully mediated by feeding self-efficacy and feeding outcome expectancy. Infant feeding problems are associated with depressive symptoms in mothers. Health professionals could work with depressed mothers to enhance infant feeding by targeting feeding self-efficacy and feeding outcome expectancy.
•Maternal depressive symptoms were associated with less responsive feeding.•Feeding self-efficacy and outcome expectancy are mediators between maternal depression and responsive feeding.•Targeting depressed mothers’ feeding self-efficacy and outcome expectancy could improve their infant feeding.
We developed a preconcentration method in which aerosol droplets containing enriched perfluorinated sulfonic acids (PFSs) are generated through bubble bursting and collected. The droplets were ...subjected to PFS analysis of perfluorohexane sulfonic acid (PFHxS) and perfluorooctanesulfonic acid (PFOS) through surface‐assisted laser desorption/ionization‐time‐of‐flight mass spectrometry; silver nanoplates (AgNPts) were assisting materials. The method was highly efficient, with an approximately three‐order magnitude enhancement (5 × 10−13 to 1 × 10−11 M). Ultralow PFS concentrations (0.5 ng/L of PFOS; 0.4 ng/L of PFHxS) were detected in preconcentrated tap water containing PFSs. Our method has potential for rapid real‐world PFS detection in water.
Aim
To develop a hospital‐based nursing human capital model for Taiwan.
Background
Effective nursing management only becomes possible when nurse managers are able to manage and maintain the right ...equilibrium among human capital components.
Method
We developed an analytic hierarchy process (AHP) model with 8 dimensions and 31 indicators based on extensive literature review and experts’ perceptual assessment. We used expert and purposive sampling and invited 82 nursing professionals to rate the importance of these dimensions and indicators. The AHP process was performed to identify the weightage and prioritize the dimensions and indicators of the nursing human capital.
Results
Our analysis showed that, for nursing human capital, health was the most important factor (weight: 34.8%), followed by employee protection (20.4%), work attitude (13.7%), employee stability (10.8%), general nursing training (6.3%), competencies (5.8%), advanced nursing training (4.3%) and clinical nursing experience (3.9%).
Conclusion and Implication for Nursing Management
The model would be most useful for nurse administrators in long‐range strategic management. Specifically, the model can be used as a reference to form a rating system to analyse nursing human capital. Health promotion programs and employee protection measures targeting nurses could improve nursing human capital in hospitals.
Inappropriate dietary intake during pregnancy is a key factor in low birth weight (LBW). This study compares LBW between healthy and processed dietary patterns by focusing on women of advanced ...maternal age. A cross-sectional survey was conducted with 327 postpartum women in Taiwan. The participants were assigned to two groups according to their age (≥35 years, n = 151; and 20−34 years, n = 176). An online questionnaire asked women how often they consumed 27 food items during their pregnancy. The prevalence of LBW was higher in the processed dietary pattern (79.3%) than in the healthy pattern (13.78%, p < 0.001). LBW was positively correlated with advanced maternal age (≥35 ages), low pre-pregnancy weight (BMI less than 18.5 kg/m2), insufficient gestational weight gain (GWG), and processed dietary patterns. Older mothers were 5.8 times more likely to have infants with LBW (odds ratio = 5.8; 95% confidence interval 2.0−16.6). A processed dietary pattern was 9.4 times more likely to result in LBW. Insufficient GWG was significantly positively associated with LBW (OR = 4.0; 95%CI 1.4−11.6). Maternal diet during pregnancy is an important modifiable factor for LBW. Prenatal advice should emphasize optimal nutrition, especially in older and underweight women.
To enable area-selective atomic layer deposition (AS-ALD), self-assembled monolayers (SAMs) have been used as the surface inhibitor to block a variety of ALD processes. The integrity of the SAM ...throughout the ALD process is critical to AS-ALD. Despite the demonstrated effectiveness of inhibition by SAMs, nucleation during ALD eventually occurs on SAM-protected surfaces, but its impact on SAM structures is still not fully understood. In this study, we chose the octadecyltrichlorosilane (ODTS) SAM as a model system to investigate the evolution of crystallinity and structure of SAMs before and after ALD. The breakdown behavior of SAMs when exposed to ZnO and Al2O3 ALD was systematically studied by combining synchrotron X-ray techniques and electron microscopy. We show that the crystallinity and structure of ODTS SAMs grown on Si substrates remain intact until a significant amount of material deposition takes place. In addition, the undesired ALD materials that grow on ODTS SAMs present contrasting morphologies: dispersed nanoparticles for ZnO while relatively continuous film for Al2O3. Lastly, substrate dependency was explored by comparing a Si substrate to single-crystal sapphire. Similar results in the evolution of SAM crystallinity and formation of ALD nuclei on top of SAM are observed in the ODTS–sapphire system. This study provides an in-depth view of the influence of ALD processes on the SAM structure and the nucleation behavior of ALD on SAM-protected surfaces.
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